Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK.
Pharmaceutics. 2011 Jul 13;3(3):406-24. doi: 10.3390/pharmaceutics3030406.
Four guanidine derivatives of N4,N9-diacylated spermine have been designed, synthesized, and characterized. These guanidine-containing cationic lipids bound siRNA and formed nanoparticles. Two cationic lipids with C18 unsaturated chains, N1,N12-diamidino-N4,N9-dioleoylspermine and N1,N12-diamidino-N4-linoleoyl-N9-oleoylspermine, were more efficient in terms of GFP expression reduction compared to the other cationic lipids with shorter C12 (12:0) and very long C22 (22:1) chains. N1,N12-Diamidino-N4-linoleoyl-N9-oleoylspermine siRNA lipoplexes resulted in GFP reduction (26%) in the presence of serum, and cell viability (64%). These data are comparable to those obtained with TransIT TKO. Thus, cationic lipid guanidines based on N4,N9-diacylated spermines are good candidates for non-viral delivery of siRNA to HeLa cells using self-assembled lipoplexes.
已设计、合成并表征了 4 种 N4,N9-二酰化精脒的胍基衍生物。这些含胍的阳离子脂质可与 siRNA 结合并形成纳米颗粒。与具有较短 C12（12:0）和超长 C22（22:1）链的其他阳离子脂质相比，具有 C18 不饱和链的两种阳离子脂质 N1,N12-二脒基-N4,N9-二油酰基精脒和 N1,N12-二脒基-N4-亚油酰基-N9-油酰基精脒在 GFP 表达减少方面更有效。在血清存在的情况下，N1,N12-二脒基-N4-亚油酰基-N9-油酰基精脒 siRNA 脂质体导致 GFP 减少（26%）和细胞活力（64%）。这些数据与 TransIT TKO 获得的数据相当。因此，基于 N4,N9-二酰化精脒的阳离子脂质胍是使用自组装脂质体将 siRNA 非病毒递送至 HeLa 细胞的良好候选物。
